Inflammation is a basic pathophysiologic process that is defined as the reaction of vascularized living tissue to local injury. The inflammatory process is important to the host because it serves in the process of repair of the injury and destruction of pathogenic organisms and tumors but sometimes inflammation may be harmful when it continues unchecked, as in rheumatoid arthritis. The detection of the inflammatory process is important to physicians because it indicates the presence of significant illness or injury. Examples of illnesses often characterized by significant inflammation are myocardial infarction, active tuberculosis, osteomyelitis (bone infection), rheumatoid arthritis, cholecytistis (infected gall bladder), and pyelonephritis (infected kidney), and disseminated cancer among others.
Patients who have significant inflammatory processes often have signs and symptoms of inflammation that are well known, such as fever, fatigue, loss of appetite, low blood pressure, and sometimes abnormalities in the amount of circulating white blood cells including both elevation and depression of their numbers, but these signs and symptoms are neither sensitive nor specific to the presence of inflammation. Many diseases and physical conditions, such as those listed above will cause inflammatory responses which can be noted in the blood. These inflammatory responses can frequently occur before more specific signs and symptoms of disease can be identified, and thus the detection of the presence of inflammation may allow more prompt diagnosis and treatment of the underlying condition. The best known and most widely used blood test indicator of inflammation is the erythrocyte sedimentation rate or ESR. The ESR was discovered by Fahraeus and popularized and improved by Wintrobe and Westergren. The Westergren erythrocyte sedimentation rate, or Westergren ESR, or WESR, which is sensitive to global elevations in inflammatory proteins is performed by measuring the distance the erythrocytes have sedimented in 60 minutes in a sample of anticoagulated blood which has been placed in a 200 mm long tube of defined dimensions. It has been an enduring laboratory test for both screening patients on an initial visit to a physician, and for following the evolution of the inflammatory condition in return visits. Despite the widespread use of the ESR procedure, there are certain drawbacks to this test which relate to, among other things, the amount of blood used to perform the test (at least one milliliter, which is a large amount for an infant); the amount of time needed to perform the test (one hour), and the fact that the test should optimally be performed within two hours of obtaining the blood. The ESR performed in the manner described by Wintrobe and Westergren is also affected by factors that may not indicate the presence or absence of inflammation such as: the presence of abnormally shaped red cells; the presence of proteins affecting the viscosity of the blood; the presence of antibody or cold agglutinens directed against red blood cells; the general level of gamma globulins even if they are not directed against the red cells; and deviations from verticality of the ESR tube while the test is being performed, as well as ambient temperature and vibration. Physicians therefore have attempted to develop other tests for inflammation that may be easier or quicker, or more sensitive or specific. Such tests include the C reactive protein or CRP; the white blood cell count; the granulocyte count (a component of the white blood cell count); the orosomucoid protein; the hematocrit or hemoglobin; and the fibrinogen. A total of at least sixteen tests have been used to monitor inflammation. All of these tests have advantages, as well as disadvantages, but none of them have been shown to be superior to the ESR.
It would be highly desirable to have a procedure for ascertaining the level of systemic inflammation; and which procedure requires only a small sample of blood; and which procedure can be relatively quickly performed or which procedure may be performed after a period of several hours if necessary; and which procedure is not adversely affected by abnormal blood conditions that skew the results of the ESR.